New
York Times Magazine (November 21, 2004)
The Antidepressant Dilemma.
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We were on
our way back from Mark and Cheryl's Wednesday-night Bible-study class. I was
riding with Mark, who had come straight from the advertising agency where he
works as a vice president and creative director. A young-looking 55, with
neatly combed hair and wire-rimmed glasses, he was wearing a striped Polo
button-down and pressed blue jeans. A few minutes later Mark eased his white
Volvo into the garage of their home, a meticulously decorated two-story Tudor
in Overland Park, Kan. The Millers moved here from Lenexa, like Overland Park a
suburb of Kansas City, in the summer of 1996, though they'd been talking about
relocating for years. They liked Lenexa, but Mark was doing well, and they
could afford a bigger house in a more upscale neighborhood.
Their new home
was only 30 minutes away from their old one, but it meant a new school district
for their two children. Their 15-year-old, Jenny, was going to be a freshman in
high school and was nervous about the move. Her 12-year-old brother, Matt, a
slight, fair-haired boy who wore skateboard-style clothing, was excited. As a
Cub Scout, he had built the fastest pine-wood derby car in his age division,
and he was looking forward to taking flying lessons at a flight school near
their house when he turned 14.
School
started, and Jenny was doing fine. She tried out for the drill team, and while
she didn't make it, she did meet some new friends at the auditions. Things were
a little harder for Matt at Harmony Middle School. First of all, it was big;
the Overland Park area had become very popular in recent years, and Harmony had
been forced to temporarily accommodate 700 students, nearly twice as many as it
had been designed to. Starting in the seventh grade also put Matt at a
disadvantage, as most of his classmates had already been together for a year.
Though he was small for his age, Matt was popular with the girls. Still, he was
clinging to his old friends more tightly than the Millers had hoped. On
weekends, Mark and Cheryl often found themselves driving him to and from
Lenexa.
For a while,
the Millers thought Matt was just going through a normal period of adjustment;
a few months in, though, they noticed a change. ''At the beginning of the
school year, Matt was getting calls from girls all the time,'' Cheryl, a petite
woman in a stylish gray jacket and black pants, told me. ''But around Christmas
we saw things weren't connecting for him as well. The kids weren't letting him
in. He started getting quiet, withdrawn.'' The Millers' theory is that the
other boys were jealous. ''We think some of the guys were blocking him out
because all of the girls were calling him,'' Mark said. ''He probably crossed
somebody with someone's girlfriend.''
By midwinter
the signs were more pronounced. His grades were falling. Always an A-B student
-- he had excelled in math in particular -- he now had a D and an F. In
February, Matt was caught forging his father's signature on several midterm
progress reports. The Millers were called to the school for a conference. As
the second semester continued, Matt's problems multiplied. One of his teachers
reported that Matt was breaking pencils in class and failing to interact with
his classmates. Several instances of ''unsatisfactory conduct'' were brought to
the attention of the principal.
In April, the
school put Matt in a special-needs class for an hour every afternoon. Neither
his attitude nor his behavior improved, though he did start going steady with a
girl in May. Around that time, a counselor at Harmony suggested to Mark and
Cheryl that they seek therapy for Matt during the summer. The Millers, who knew
by now that Matt was unhappy though they weren't sure why, thought this was a
good idea. They were eager to help Matt while school was not in session; that
way, he could start fresh in the fall. They initially wanted Matt to see a
social worker recommended by the school, but their insurance did not cover that
therapist. In the end, they chose a psychiatrist, telling themselves that this
might be for the best in case medication was required. Matt didn't want to go.
''He said to me, 'Mom, I'm not crazy,''' Cheryl recalled. Mark added: ''I
remember telling him, 'Matt, this is good.' We would all love to pay someone to
help us work through our problems.''
On June 30,
1997, the Millers took Matt to see Dr. Douglas Geenens, a child psychiatrist
referred to them by Matt's primary-care physician. In addition to the doctor
and the Millers, both Mark and Cheryl remember there being two other people in
the room, who Dr. Geenens explained were his trainees. Matt sat silently for
almost the entire 50-minute session. Cheryl did most of the talking, sketching
out Matt's emotional deterioration since the start of the calendar year.
Matt's next
appointment with Dr. Geenens was scheduled for July 21, a Monday. Mark and
Cheryl recalled the details for me: Matt took a 30-minute test for attention
deficit disorder and spent 15 minutes filling out a Children's Depression
Inventory form, a standard tool for measuring depression in kids. At the end of
the session, Dr. Geenens suggested that Matt try Zoloft. He gave the Millers
three sample bottles with seven 50-milligram tablets in each and told them to
make sure that Matt took one a day. The Millers had never heard of it. ''The
only thing I was aware of was Prozac,'' Cheryl told me. ''I asked him why are
you prescribing Zoloft?'' Dr. Geenens answered that Zoloft was newer and more
refined than Prozac. Cheryl asked if there were any possible side effects. Dr.
Geenens said they should be on the lookout for stomachaches or insomnia. The
doctor had no appointments available until the middle of August, but he wanted
the Millers to call in a week and let him know how Matt was doing.
Two days
later, Mark took the kids to visit his mother at her apartment in Sioux City,
Iowa. Their plan was to spend a few days there, then bring Mark's mom back to
Overland Park for the weekend -- they had tickets to a play in Kansas City --
before dropping her back home on their way to a family vacation on a lake in
Wisconsin. Matt spent much of his time in Sioux City swimming in the pool at
his grandmother's apartment complex. They came back on Friday and all went out
to dinner. ''He was sitting across from me, and I remember asking him to quit
stomping on my feet,'' Cheryl told me. ''I think back to that now -- he
couldn't sit still.'' At lunch after church a couple of days later, Matt's
grandmother also noticed that he seemed restless and agitated.
The Millers
were leaving early Monday morning for Wisconsin. On Sunday night, July 27, at
around 11:30, Matt was still on the phone with his girlfriend. Mark went to his
son's room to tell him to hang up and go to bed. ''I didn't yell at him, but I
was firm,'' Mark recalled. Matt threw the phone down and angrily slammed the
door in his father's face, something he'd never done before. Mark went back to
his room and asked Cheryl if he should go back in and talk to him. Cheryl
thought they ought to wait until the morning. ''He's finally just getting
settled,'' she told Mark. ''We don't want to rile him up again.'' When Cheryl
went in to wake Matt up the following morning, she found him hanging by a belt
from a laundry hook in his closet.
It didn't
take long for Mark's thoughts to turn to the Zoloft: ''It was the only thing
that had changed that week. What else could we attribute it to? He's on a new
medication, and he takes his life.'' When he spoke with Dr. Geenens later that
morning, Mark asked if there was something in the drug that might have
triggered suicidal behavior. The doctor told him that he wasn't aware of
anything.
At the time, there wasn't much reason for Dr. Geenens to have known otherwise.
Over the course of the past two years, however, the debate over whether
antidepressants, particularly those known as S.S.R.I.'s -- selective serotonin
reuptake inhibitors -- can trigger suicidal behavior in teenagers has migrated
from the margins of the medical community to the front pages of newspapers.
Adding to the controversy was public outrage at revelations that a number of
pharmaceutical companies had deliberately withheld damning information about
S.S.R.I.'s -- specifically, data from clinical trials that suggested that these
drugs were both more dangerous and less effective for adolescents than millions
of consumers had been led to believe.
Beneath the
rancor was a complicated question. Patients who were being prescribed
antidepressants were, by definition, vulnerable to suicidal behavior; it was
difficult to determine where the effects of depression ended and the effects of
the drug began. What's more, psychiatrists had been aware for decades that the
risk of suicide increases when patients first start emerging from depression.
Rollback, as this is known, is thought to be caused by a depressed patient's
energy level rising ahead of his or her mood. No longer lethargic but still
deeply unhappy, for a brief period some patients who had been too apathetic
before to harm themselves now had the wherewithal to do so. Were patients
taking S.S.R.I.'s experiencing rollback? Or was there something specific about
S.S.R.I.'s that triggered suicidal impulses?
Things came
to a head this fall with the F.D.A.'s affirmation of a link between
antidepressants and suicide ''ideation,'' or suicidal thoughts, in adolescents.
Now all antidepressants, including S.S.R.I.'s like Prozac, Zoloft, Paxil,
Lexapro, Luvox and Celexa, must carry a black-box warning label, the regulatory
agency's strongest kind, making a possible suicide link explicit and all but
ensuring a significant decrease in their use among young people. Far from
providing closure on this complicated issue, though, the F.D.A. ruling may
ultimately raise more questions than it answers.
Many child
psychiatrists, who as a group have come to rely on S.S.R.I.'s to treat
adolescent depression, seem to think the F.D.A. overreached. Studies have shown
that one out of every 20 teenagers has suffered at least one bout of severe
depression in his or her life, and adolescent depression can be especially
difficult for doctors to manage. Teenagers are often resistant to
psychotherapy, and unlike adults, who can quit a job or leave a marriage that
might be aggravating their unhappiness, adolescents are almost always stuck
with their lots. Doctors who treat young people -- child psychiatrists,
pediatricians and general practitioners alike -- were wary of tricyclics, the
previous generation of antidepressants, because of the risk of overdose. (The
difference between an effective dose and a lethal one could be as small as six
tablets.) But it is much harder to OD on S.S.R.I.'s. While the F.D.A. has
approved only Prozac for depression in children and adolescents, doctors are
free to prescribe any of these drugs ''off label'' for a patient group not
specified on the packaging. And they have: between the early 90's and 2001, the
prescription rate of antidepressants for those under 18 more than tripled. In
2002, 11 million antidepressant prescriptions were written for children and
adolescents in the United States. Doctors recommended the drugs primarily to
treat depression, but also for other emotional problems, from anxiety to
shyness to obsessive-compulsive disorder.
The
pharmaceutical companies are clearly making a product that most psychiatrists
consider critical to treating depressed adolescents. Not prescribing these drugs
may very well pose a greater threat than prescribing them. Studies have shown
that areas in which antidepressant use among young people is widespread have
experienced a dip in teenage suicide rates; according to Dr. John Mann, a
suicide expert at Columbia University, fewer than 20 percent of the 4,000
adolescents who commit suicide in America each year are taking or have ever
taken antidepressants. ''It would be ludicrous to think that antidepressants
could actually contribute to suicide in the United States in any kind of
significant way,'' Mann told me. ''The vast majority of teen suicides are
actually committed in the absence of antidepressants.''
The F.D.A.
was essentially forced to strike a balance between the cost of the few and the good
of the many. Did the agency give too much weight to the few? ''For a family who
has lost a child shortly after going on Prozac or some other S.S.R.I., I don't
know what I can say to them,'' Dr. John Walkup, a child psychiatrist in
Baltimore, told me. ''But it's dangerous to make public policy based on rare
and tragic events.'' Still, as Mark and Cheryl Miller will tell you, it's no
less dangerous to ignore them.
In the months after Matt's death, the Millers confronted a sort of grief that
most parents cannot begin to imagine. Both of them took a month off from work.
They started every day with an early-morning walk around a lake near their
house. They talked about Matt and all of the things they might have done
differently. Jenny made the drill team that fall, and the Millers attended
every Friday-night football game to watch her perform at halftime. They found
that they felt better when they were out of the house, so they took lots of
weekend trips and visited family members on Thanksgiving and over Christmas.
They also went out with friends and colleagues as much as possible. ''We both
strived for normalcy again, which we knew would never be quite the same,'' Mark
told me. Always religious people, the Millers immersed themselves even deeper
in Christianity and met weekly with a Christian grief counselor.
But Mark was
also hunting for answers. He soon found what he was looking for, or rather
whom. During one Internet search, he happened across the Web site of Ann Blake
Tracy, author of ''Prozac: Panacea or Pandora?'' a self-published 424-page
screed against S.S.R.I.'s. Unless you are desperate, as most people typing
words like ''suicide'' and ''antidepressants'' into Google most likely are,
Tracy's Web site does not invite lingering. A picture of her in what looks like
an out-of-focus 70's yearbook photo is surrounded by text that is the online
equivalent of someone yelling outside the gate of the White House -- angry
black-and-red type interrupted with WARNINGS about the dangers of going off
these drugs cold turkey, and invitations to ''click here'' to read more
personal horror stories.
Even among
the most ardent opponents of S.S.R.I.'s, Tracy is an extremist. When I met her
this fall, she told me that she began her campaign against antidepressants in
1989, when two friends in Salt Lake City, both Mormons, became alcoholics
shortly after going on Prozac. Since then, she has come to believe that
antidepressants have played a role in just about every high-profile act of
violence the world has seen, from the death of the Princess of Wales (''When
Princess Di was killed,'' she said, ''I called the police in Paris and said
you've got a driver on Prozac'') to the 1999 shootings at Columbine High School
to the terrorist attacks of Sept. 11. But as an early anti-S.S.R.I. activist,
Tracy was a godsend to families like the Millers, who were relieved to discover
someone who could vindicate their hunch about these drugs.
Mark pulled
Tracy's number from her Web site and called her. After hearing Matt's story,
she steered Mark to some other sources, and he continued his research. He soon
learned that the possibility of a link between S.S.R.I.'s and suicide had first
been raised many years earlier by two Harvard Medical School psychiatrists, Dr.
Martin Teicher and Dr. Jonathan Cole, in a paper published in early 1990 in The
American Journal of Psychiatry titled ''Emergence of Intense Suicidal
Preoccupation During Fluoxetine Treatment.'' The doctors observed that six of
their adult patients experienced ''intense, violent suicidal preoccupation''
within two to seven weeks of starting on fluoxetine, the generic name for
Prozac, the first of the S.S.R.I.'s to reach the American market.
Teicher and
Cole didn't want to overstate the significance of their findings -- five of the
six patients had entertained thoughts of killing themselves at some point
earlier in their lives -- but the onset of suicidal thinking had occurred so
suddenly after the beginning of treatment that a prospective link was hard to
ignore. ''The purpose of this report is to suggest the surprising possibility
that fluoxetine may induce suicidal ideation in some patients,'' the doctors
wrote, reporting that the phenomenon appeared in about 3.5 percent of their
patients taking the drug.
About a year
later, Dr. Robert A. King, a child and adolescent psychiatrist at the Child
Study Center at Yale Medical School, noticed something similar in several of
his patients between ages 10 and 17. Dr. King had prescribed Prozac for 42 of
his young patients suffering from obsessive-compulsive disorder (but not
depression), 6 of whom experienced what he later described in The Journal of
the American Academy of Child and Adolescent Psychiatry as ''self-injurious
ideation or behavior'' -- behavior that none of them had ever experienced
before. This was too small a sample to rule out the possibility of coincidence,
but large enough for Dr. King to conclude that a narrow, still poorly defined
group of patients on Prozac do seem to experience a range of adverse side
effects from restlessness to self-destructive acts.
In September
1991, the F.D.A. convened a committee of 10 psychiatrists and psychologists to
weigh in on the issue. After listening to hours of testimony from victims,
depression experts and mental-health professionals, the panel decided that more
research was needed but that for now there was no ''credible evidence'' of a
link..
To Mark, this
hardly sounded like a clean bill of health. Other things troubled him as well.
He learned, for instance, that the F.D.A. had never approved Zoloft as a
pediatric antidepressant -- and indeed that the drug's maker, Pfizer, had not
been compelled to prove that it was safe for young people. He read about a
phenomenon known as akathisia, or activation, a state of extreme agitation that
can be induced by some psychotropic medications and can cause patients to
behave in an uncharacteristically violent manner, which seemed to describe
perfectly Matt's condition before his suicide.
Armed with
this new information, Mark contacted Matt's psychiatrist, with whom he hadn't
spoken since the morning of his son's death, and suggested that they meet. Mark
knew that most psychiatrists would also have prescribed antidepressants for
Matt, but he wanted to encourage the doctor to reconsider his approach to these
drugs. To that end, he brought along all of his S.S.R.I. files. They ordered
iced teas, and Mark said a short prayer asking that they honor Matt in their
approach to this very difficult meeting. He began by telling Dr. Geenens that
he and Cheryl blamed themselves for being too quick to embrace a ''solution in
a bottle'' to Matt's unhappiness. ''We wanted a miracle,'' Mark said to the
doctor, ''and we were willing to accept anything offered which promised an end
to his depression, and to our agony.'' Mark explained to Dr. Geenens that he
and Cheryl wanted him as a partner, not an adversary, and urged him to join
their anti-S.S.R.I. cause by using his professional influence to encourage
other physicians to exercise restraint when it came to antidepressants. In
Mark's recollection, Dr. Geenens was polite but visibly uncomfortable. When the
hour-and-15-minute meeting was over, Mark didn't get the feeling the doctor was
going to change his prescription habits, let alone enlist in their fight against
antidepressants. ''He was relieved to know I wasn't planning a malpractice
suit,'' Mark later reflected in an e-mail message to Ann Tracy. (Dr. Geenens
did not respond to phone calls seeking comment.)
Mark and
Cheryl did, however, decide to sue Pfizer. The next time Mark saw Dr. Geenens,
two years had passed and the doctor had just given his deposition in the case.
By this point, any lingering hopes that Dr. Geenens might emerge as an ally had
long vanished. Not only had the doctor not responded to letters from the
Millers' lawyer; he had also signed an affidavit for Pfizer in which he
maintained that he had relied solely on his own professional judgment when
prescribing Zoloft for Matt. At his deposition, Dr. Geenens also acknowledged
that he was a member of Pfizer's Speakers Bureau, and that he gave -- and was
still giving -- on the order of 50 Pfizer-sponsored talks a year for between
$300 and $750 each.
By the time of Matt Miller's death in 1997, there had been hundreds of adult
antidepressant lawsuits focusing on both violence and suicide, the vast
majority of which were either dismissed or resolved out of court. Drug makers
are rarely eager to settle these cases, largely because they don't want to
encourage the small cadre of trial lawyers who make a living suing them. At the
same time, the publicity involved with going to court, in addition to the risk
of confronting a guilty verdict, is even less appealing. A result is a great
many 11th-hour settlements. Indeed, as of 1997, only one antidepressant case,
that of Joseph Wesbecker, a former employee at a printing plant in Louisville
who went on a shooting spree about a month after starting to take Prozac in
1989, had ever gone to trial.
For all of
the adult suits, however, there had been relatively few adolescent cases before
Miller v. Pfizer Inc. Unlike product-liability lawsuits, which focus on whether
a particular item malfunctioned, it's the psychic state of an individual that
is contested in S.S.R.I. lawsuits. For the parents of that individual, the
prospect of subjecting themselves to a grueling emotional autopsy of their lost
child can be too much to bear.
The Millers
agonized over the decision to sue Pfizer, waiting until August 1999, two years
after Matt's death and fewer than 24 hours before the statute of limitations
would expire, before finally filing the papers. They knew that pursuing the
case was going to require considerable financial and emotional investments.
While their lawyer was working on contingency, Mark had to cover all of the
court fees, which would run into the tens of thousands of dollars. ''We knew it
was going to be painful, that we were going to be reopening all sorts of
wounds,'' Mark told me, reflecting on the decision now. ''I don't regret it. I
don't think I'd be able to live with myself if I didn't feel like we had done
everything we could for Matt. But I would tell anyone who asks me, don't do it.
It's not worth it.''
Mark and
Cheryl hired Andy Vickery to represent them. A stocky and excitable Georgia-born,
Yale-educated plaintiff's lawyer who wears black cowboy boots under his dark
suits and drives a Jaguar, Vickery has handled little besides antidepressant
cases for the past decade. This preoccupation has not made for the most stable
existence. A few years ago, after a devastating defeat at the hands of Eli
Lilly & Company -- ''The verdict came down on Good Friday, and I felt like
I'd been crucified'' -- and a succession of costly dismissals, Vickery almost
lost the ranch-style house he and his second wife bought and renovated in
Houston's tony Tanglewood section, a few blocks away from former
But there
have been some big victories since. In addition to dozens of settlements -- the
out-of-court agreements always stipulate that the terms remain undisclosed --
Vickery took GlaxoSmithKline to court on behalf of the relatives of Donald
Schell, who went on a violent rampage hours after starting on the company's
S.S.R.I. Paxil, murdering his wife, his daughter and his granddaughter before
turning the gun on himself. In 2001 a Wyoming jury ordered the company to pay
$6.4 million to Schell's relatives, 40 percent of which went to Vickery, who
paid off his mortgage.
Like any good
trial lawyer, Vickery has internalized his clients' traumas and converted them
into a cause. ''We're on the right side, we've been on the right side all along
and now the world is starting to realize that we are on the right side,'' he
told me in his office in a Houston skyscraper last month. ''I've believed it from
the bottom of my heart all along.''
The basic
facts of the Miller case looked compelling to Vickery. It was a violent
suicide, which fit the pattern he had observed in previous antidepressant
cases. Also, Matt had hanged himself from a low-hanging hook; all he had to do
was lower his feet to the floor and he would have saved himself. To Vickery,
this suggested a sudden, drug-induced mania. ''Matt Miller went from zero to 60
and hanged himself in a way that took Herculean effort,'' he told me.
Miller v.
Pfizer Inc. was Vickery's second adolescent suit and his first suit against
Pfizer. He had tangled with enough drug companies to know it wasn't going to be
easy, but he soon found himself grappling with a uniquely ferocious enemy. In
addition to interviewing virtually everyone whom Matt had come into contact
with in the year leading up his death, Pfizer burrowed deep into Mark and
Cheryl's private life. The company's lawyers deposed the Millers' pastor and
grief counselor, and subpoenaed the handwritten journal that Cheryl kept after
her son's suicide as well as their daughter Jenny's diary. Pfizer even hired
Park Dietz, a forensic psychiatrist and an expert in autoerotic asphyxiation,
to file a report contending that Matt's suicide may have been a case of
masturbation gone awry. Among the numerous other possible causes Pfizer raised
during the pretrial proceedings, according to Vickery, was Matt's relationship
with his father. Malcolm Wheeler, Pfizer's lead attorney, ''said in open court
that Matt Miller hated his father,'' Vickery said. ''That's as low a blow as
I've ever seen by any lawyer. . . . They are subhuman. I hate Pfizer.''
Pfizer
doesn't think much more of Vickery. ''Andy is a very clever, articulate guy,''
Wheeler told me recently. ''But he just throws stuff out there, and unless you
compel him to provide the backup data and calculations, he'll just talk you to
death.''
The Millers' story of Matt's life, until its abrupt end, is one of a more or
less normal adolescent boy experiencing more or less normal adolescent
problems. The Pfizer lawyers set out to build a counternarrative. In the
thousands of pages of depositions and expert-witness reports, there are moments
when it seems that the Millers might not have grasped the depth of their son's
emotional problems. ''Matt Miller was a very, very tragically disturbed child
who just didn't get help in time,'' as Wheeler put it.
That said,
many of the details that Pfizer's lawyers brought out can be seen either as a
serious indication of severe emotional problems or as standard teenage acting
out. The only thing that's truly beyond dispute is that the emotional life of
an adolescent boy is virtually impossible to parse.
Matt was
clearly having trouble making friends at Harmony Middle School. One of his
guidance counselors testified that other students described him as ''weird,''
and noted that Matt had a tendency to alienate the more popular kids and to
pick on the less popular ones. Still, a good deal of his behavior seems fairly
typical for an attention-seeking teenage boy, things like baiting other
students, joking about defecation, drawing lewd pictures. Matt's special-needs
instructor, Roxana Rogers, recalled Matt breaking into tears during a
conversation in the hallway because he felt so much pressure at home to be
''perfect,'' also not an entirely unusual sentiment for the child of ambitious
upper-middle-class parents.
Yet there
were hints of violence and self-destructiveness as well. Matt was disciplined
several times at school, once for hitting a classmate with a chain, another
time for supposedly threatening a fellow student with a piece of a plastic
mirror. Rogers once saw Matt banging his head against his locker and remarked
in her deposition that he shuffled his feet and walked around the classroom at
inappropriate times -- which sounds a lot like the sort of restlessness that
Cheryl observed the week he was on Zoloft.
There was
every indication that Matt was depressed. He scored a 13 on the Children's
Depression Inventory, which Dr. Geenens considered ''significant'' and
indicative of moderate depression. There was also evidence that he had talked
about taking his own life before doing so. Chad Brownel, Matt's only close
friend at Harmony, said that Matt mentioned suicide ''hundreds of times''
during the six months that they'd known each other. And toward the end of the
school year, when Roxana Rogers asked Matt about his plans for the summer, Matt
said that if his parents sent him away to camp, he would kill them and then
kill himself. Rogers considered the remark and his behavior problematic enough
to call his mother and schedule a meeting.
What's more
difficult to determine is whether Matt would have acted on these thoughts had
he not taken Zoloft. Suicidal ideation is common among depressed adolescents,
but completed suicides are rare; some child psychiatrists have come to see
suicide attempts more as appeals for help than as expressions of a
determination to die. One question on Matt's Children's Depression Inventory
asked him to choose one of the following: ''I do not think about killing
myself''; ''I think about killing myself, but I would not do it''; ''I want to
kill myself.'' Matt answered that he thought about killing himself but would
not do it.
After going
on the medication, Matt told his friend Chad that the pills were giving him
insomnia. Chad also noticed that Matt seemed ''a little more wild'' and more
energetic. Instead of watching ''Beavis and Butt-head'' or playing the video
game Mario Kart, which they usually did, Matt wanted to ride bikes to Taco
Bell. Matt could have been going through rollback, a relatively common reaction
in the early stages of treatment. Or he might have been experiencing
activation, the dangerous side effect that Mark had read about online. Was it
the Zoloft per se? Or was Matt's suicide a tragic by-product of the process of
getting better?
Those were
questions for the jury to wrestle with. But before Miller v. Pfizer Inc. could
go to trial, Vickery had to show general causation -- in other words, that
S.S.R.I.'s cause some people to become violent or suicidal. He had done this in
all of his previous antidepressant cases. There had been no shortage of
hard-fought battles -- for the drug makers, causality was their first line of
defense -- but he had never failed to clear that hurdle.
Vickery
turned to Dr. David Healy, an expert witness whom he had used several times
before, to present the court with proof of a plausible link between S.S.R.I.'s
and suicide ideation. A specialist in psychological medicine at Cardiff
University in Wales, Dr. Healy had first warned about the potential for
suicidal acts among patients on antidepressants in 1990. Since then he has
published several provocative academic books on the subject, most recently
''Let Them Eat Prozac''; as a frequent expert witness in S.S.R.I. cases, Dr.
Healy has spent quite a bit of time rooting around in the basements of drug
companies searching for suppressed information on antidepressants. Conversely,
the drug companies have spent quite a bit of time and money attacking Dr.
Healy's bona fides and trying to discredit his research as ''junk science.''
The judge
appointed two independent medical experts to evaluate Dr. Healy's work. Dr. Healy
submitted his data to the court. The experts were flown to Kansas City. Over
two days of hearings, they raised questions about Dr. Healy's methodologies,
and the judge ultimately barred his testimony. Without it, the Millers had no
proof of a causal link. Their case was dismissed before it had even begun.
Last
February, six months before the F.D.A. acknowledged a link between S.S.R.I.'s
and suicidal thoughts, a Kansas appeals court affirmed the ruling. By this
point, Vickery had spent more than $200,000 on the Millers' suit. One final,
long-shot option remained: the Supreme Court.
Mark and Cheryl's lawsuit may have been foundering, but they were finally
making some headway in their public campaign against S.S.R.I.'s.
Not long
after Matt's death, Mark helped Ann Tracy create a Web site for her nonprofit
group, the International Coalition for Drug Awareness, where families with
similar experiences could post their stories and learn more about the side
effects of antidepressants. He soon found himself at the center of a growing
community of ''survivors.'' For several years, this loose network of families
tried vainly to draw attention to their cause; but then in late 2003, when the
Medicines and Healthcare products Regulatory Agency -- the U.K.'s equivalent of
the F.D.A. -- advised against the use of all S.S.R.I.'s except Prozac in
patients under 18, the outside world suddenly became interested.
The British
decision had been the unintended consequence of GlaxoSmithKline's request to
market Seroxat -- known as Paxil in the United States -- to children with
social phobias and O.C.D. As part of the application process, GlaxoSmithKline
submitted what it believed to be all the data required for approval. The
M.H.R.A., however, wanted to see more, specifically all of the company's trials
on Paxil and adolescent depression, many of which had never been published.
The trials
were submitted, and the British regulatory agency did not like what it saw. Not
only did the data suggest that Paxil caused an increased suicide risk in
children; several of the trials also failed to demonstrate that the drug
performed any better than a sugar pill. Within a matter of weeks, the M.H.R.A.
publicly announced that Paxil should not be used in children. Not long after
came the broader warning against all antidepressants except Prozac.
By this point
the F.D.A. had also seen GlaxoSmithKline's unpublished Paxil data and was deep
into an investigation of its own. Over the summer of 2003, the regulatory
agency warned doctors against using Paxil in children under 18, and in the fall
of that year it publicly acknowledged that it couldn't ''rule out'' the
possibility that a number of other antidepressants might also increase the risk
of suicide in adolescents.
For the most
part, though, the F.D.A. approached the issue more gingerly than its British
counterpart. Agency officials wanted to see additional data before taking any
further action. The problem was that no large-scale studies existed. Until they
did, the F.D.A.'s only option was to combine a number of small, disparate
trials conducted by drug makers in the late 90's and try to draw some
meta-conclusions. None of those trials had been designed to assess suicide
risk, but for the time being they were all that the agency had to go on.
In late 2003,
the F.D.A. asked the pharmaceutical companies for all relevant information on
every so-called adverse event in each of these pediatric antidepressant trials.
A group of independent researchers from Columbia University was commissioned to
review the 427 cases the companies produced. With the help of a separate team
of suicide experts, the Columbia researchers set about classifying them as
suicidal or not.
It was not an
easy task. There wasn't a single successfully completed suicide among the cases
provided, which meant that the researchers had to decipher suicidal thoughts or
actions based on brief, vague narratives. Also, the information the researchers
were given was often misleading. For instance, one child had taken 11 pills
impulsively before going to school; this was classified a medication error.
Another had wrapped a cord around his neck; this was labeled ''hostility.'' At
the same time, relatively harmless acts -- including a girl slapping herself in
the face -- had been listed as ''suicidal.'' But the biggest challenge was a
theoretical one. ''There's a lack of conceptual clarity about how you even
define a suicide attempt,'' said the principal investigator of the Columbia
team, Kelly Posner. Self-mutilation, for example, is common among depressed
children, but how can you know whether it was done with suicidal intent?
The F.D.A.
did not want to issue a ruling until the Columbia group finished, but one
F.D.A. drug-safety analyst, Andrew Mosholder, did not want to wait. Mosholder
was assigned to review GlaxoSmithKline's Paxil trials many months earlier and
noticed that a number of events that looked a lot like suicide attempts had
been subsumed under the euphemistic term ''emotional lability.'' Since then he
had conducted his own analysis on several antidepressants and determined that
children on them were almost twice as likely to experience suicidal thoughts or
exhibit suicidal behavior as those taking placebos. Mosholder wanted to go
public, but the F.D.A. wouldn't allow it, out of concern that his conclusions
would only further fan the flames.
Mosholder's
findings were soon leaked to The San Francisco Chronicle. Before long, the
story was splashed across the nation's newspapers. Families like the Millers
had a new hero, a would-be whistle-blower who had been silenced by his own
government.
The publicity
surrounding Mosholder's conclusions also piqued the interest of several
politicians, most notably Senator Charles Grassley of Iowa, who wondered if the
F.D.A. might be deliberately suppressing information about the dangerous side
effects of antidepressants. Tom Torlakson, a state senator in California whose
niece had committed suicide after starting on Celexa, convened his own hearings
on the issue. In New York, Attorney General Eliot Spitzer sued GlaxoSmithKline
for concealing vital information from the public about the safety and efficacy
of Paxil. (The two parties settled, with the company agreeing to pay $2.5
million to New York State.)
In the middle
of September, with the Columbia study complete, the F.D.A. convened hearings on
the issue. The anti-S.S.R.I. lobby was galvanized; dozens of families came to
Maryland to tell their harrowing tales. (Only one mother rose to defend the
drugs.) Kathleen Bodnar spoke about her 21-year-old daughter -- Torlakson's
niece -- who threw herself in front of a BART train in San Francisco last
spring, shortly after being prescribed Celexa. A number of families blasted the
drug makers for suppressing data and chided the F.D.A. for not taking stronger
steps earlier. ''The blood of these children is on your hands,'' Mathy Downing,
who found her 12-year-old daughter hanging from the valance above her bed in
January, a few days after taking 100 milligrams of Zoloft, told the panel.
But for all
of the impassioned testimony, the most important presentation came from an
F.D.A. medical reviewer, who offered his analysis of the long-awaited Columbia
review. The risk of depressed children engaging in suicidal acts was 1.78 times
greater for those who had been treated with antidepressants than for those who
had been given placebos. At the end of the hearings, the panel voted to add to
all antidepressants black-box warnings cautioning that the drugs can trigger
suicidal behavior in adolescents. ''A 'BLACK BOX'! -- Wow,'' Mark wrote in a
mass e-mail message to fellow survivors. ''Could we have ever guessed they
would go this far?''
When I
visited Mark and Cheryl in late September, they were optimistic that the F.D.A.
ruling would breathe new life into the their lawsuit against Pfizer. ''The
whole summary judgment was granted based on us not being able to prove that
there is evidence of suicidality,'' Mark told me. ''Now the F.D.A. has
basically validated our position.''
A couple of
weeks later, though, the Millers' five-year battle with Pfizer was over. The
Supreme Court declined to review their case.
The black-box warning seems
sure to put off parents, not to mention doctors, who will now have to assume a
greater share of the responsibility when prescribing these drugs. ''A black box
is scary,'' Dr. Walkup, the Baltimore psychiatrist, told me. ''In order for you
to go against it, you've got to summon a certain amount of courage.''
While many
child psychiatrists are unlikely to change their attitude toward S.S.R.I.'s,
most pediatricians and general practitioners, who until now have written the
bulk of these prescriptions, no doubt will. This could mean a lot of untreated
children. There are only 7,400 child and adolescent psychiatrists in America; even
in areas with high per-capita concentrations, the average wait to see one is
six weeks. There is also the matter of cost. Many child psychiatrists charge
steep hourly rates that are only partly offset by health insurance providers.
For doctors
who don't have much experience with S.S.R.I.'s, prescribing them for
adolescents does seem daunting. Teenagers can't always be counted on to take
their pills, and as with many medications, sudden withdrawal from S.S.R.I.'s
can be dangerous. Perhaps an even bigger challenge is teasing out bipolar from
unipolar depression, a critical distinction given that S.S.R.I.'s can trigger
mania in a small number of bipolar adolescents. Even for those children who do
respond well to S.S.R.I.'s, finding the right dose -- and, in some cases, the
right combination of drugs -- can be tricky. Some children metabolize medicine
more quickly than adults, others more slowly.
Still, over
the past few months I have spoken with a number of teenagers (and their
parents) whose lives have been saved by antidepressants. ''Had it not been for
these two medications, I would not be here,'' Kristen Conklin, a 21-year-old
graduate student at Widener University in Pennsylvania, told me. Conklin
started taking Wellbutrin five years ago after a failed suicide attempt. A year
later, her doctor added Effexor as well. ''I can look back on my life now and
know that if I had to feel that way again, I probably would think it's a smart
idea to commit suicide. It took some time to figure out what works, but they
have helped me in ways that I can't even begin to explain.''
The numerous
antidepressant success stories have none of the drama of the comparatively few
failures, but that doesn't necessarily make them any less important. Conklin's
psychiatrist, Dr. Peter Kahn, told me that he and many of his colleagues have
known from the beginning that S.S.R.I.'s are potent drugs. They always start
with low doses and raise them gradually -- their mantra is ''start low, go
slow'' -- and supervise their patients closely, particularly in the first few
weeks after beginning treatment. (Kahn makes sure that all of his patients have
his cellphone number.)
Child
psychiatrists have an almost universal faith in S.S.R.I.'s; the problem is that
there isn't much clinical data to support their conviction. Why? One
explanation is that the limited number of studies that have been done on
adolescents and antidepressants were almost all substandard. Most of them were
conducted in response to a 1997 Congressional act intended to encourage drug
makers to undertake more pediatric trials. Companies could extend their patents
for a drug for six months by testing it on children -- whether the trial
demonstrated that the drug worked or not. There was, in other words, a powerful
incentive to do the trials, but no incentive to do them well. Among other
flaws, patients were enrolled at multiple sites in a number of different
countries, which made quality control very difficult. In clinical parlance, the
trials were susceptible to a lot of ''noise,'' factors that obscure rather than
illuminate the effects of a given drug.
A much more
carefully conducted Prozac study was published this year in The Journal of the
American Medical Association. The results pleased defenders of S.S.R.I.'s: 61
percent of the patients treated with Prozac improved, compared with only 35
percent of those given sugar pills. ''This study should put to rest doubt about
whether these drugs work in teenagers with severe depression,'' said one of the
report's authors, Dr. Graham Emslie. (While the study was sponsored by the
National Institute of Mental Health, Emslie has received money from a number of
drug companies in the past.) What the study didn't do is put to rest concerns
about suicidal side effects. No patients in the control group tried to commit
suicide, while six of those treated with Prozac did.
More trials
are under way now, but it may be years until the F.D.A. will have enough fresh
data to revisit the subject. Until then, doctors will have to decide whether
they want to go up against a black-box warning. And parents will have to decide
whether they want to trust their doctor's judgment.